Antioxidant Supplementation Enhances Bacterial Peritonitis in Mice by Inhibiting Phagocytosis

J Med Microbiol. 2014 Mar;63(Pt 3):355-366. doi: 10.1099/jmm.0.067173-0. Epub 2013 Dec 4.

Abstract

Antioxidants are known to exhibit numerous health benefits including anti-ageing, anti-apoptotic and immuno-stimulatory effects. However, we present the data showing counterproductive effects of therapeutically relevant antioxidants on bacterial clearance by the immune system in a murine peritonitic model. The antioxidants ascorbic acid, glutathione and N-acetylcysteine augmented morbidity and mortality in mice carrying Eshcerichia coli-induced acute bacterial peritonitis. Treatment of peritonitic mice with antioxidants significantly increased their bacterial load in the range of 0.3-2 logs. Antioxidant administration to peritonitic mice resulted in decreased numbers of macrophages, B-cells and dendritic cells at the primary site of infection and increased neutrophil infiltration. Serum TNF-α levels were also decreased in antioxidant-treated peritonitic mice. In vitro experiments showed that antioxidants reduced the phagocytic efficacy of peritoneal macrophages by ~60-75% and also decreased E. coli-induced oxidative burst in macrophages cells. Taken together, our data indicate that the antioxidants increased the severity of peritonitis by decreasing the phagocytic efficiency, oxidative burst, and TNF-α production, and increasing neutrophil infiltration. Based on these results, we propose that antioxidant supplementation during the course of bacterial infection is not recommended as it could be detrimental for the host. In addition, the present study underlines the importance of timing and context of antioxidant administration rather than indiscriminate usage to gain the best possible therapeutic advantage of these redox compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Disease Models, Animal
  • Escherichia coli / drug effects
  • Escherichia coli / immunology*
  • Escherichia coli / pathogenicity
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / microbiology
  • Escherichia coli K12 / drug effects
  • Escherichia coli K12 / immunology
  • Female
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Neutrophil Infiltration / drug effects
  • Peritonitis / drug therapy
  • Peritonitis / immunology*
  • Peritonitis / microbiology
  • Phagocytosis / drug effects*
  • Respiratory Burst / drug effects
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / drug effects

Substances

  • Antioxidants
  • Tumor Necrosis Factor-alpha